title: Feeding the deoxyribonucleoside salvage pathway to rescue mitochondrial DNA.
abstract: Mutations in an increasing number of nuclear genes involved in deoxyribonucleotide homeostasis cause disorders associated with somatic mitochondrial DNA (mtDNA) abnormalities. Dysfunction of the products of these genes leads to limited availability of substrates for mtDNA replication and results in mtDNA depletion, multiple deletions or point mutations; mtDNA depletion is the molecular feature linked to greatest clinical severity. In this review, we discuss recent results demonstrating that enhancement of the salvage pathways by increasing the availability of deoxyribonucleosides needed for each specific genetic defect prevents mtDNA depletion. Hence, we propose administration of selected deoxyribonucleosides and/or inhibitors of their catabolism as a pharmacological strategy to treat these diseases.
authors.affiliation: Mitochondrial Disorders Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Cámara
authors.forename: Emiliano
authors.initials: E
authors.lastname: González-Vioque
authors.forename: Mauro
authors.initials: M
authors.lastname: Scarpelli
authors.forename: Javier
authors.initials: J
authors.lastname: Torres-Torronteras
authors.forename: Ramon
authors.initials: R
authors.lastname: Martí
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015316:Genetic Therapy / Q000639:trends; D006801:Humans; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000628:therapy
chemical_list: D004272:DNA, Mitochondrial; D003853:Deoxyribonucleosides